BOSTON--(BUSINESS WIRE)--
Vertex
Pharmaceuticals Incorporated (Nasdaq: VRTX) today announced the
planned initiation of two Phase 2 studies to evaluate the
next-generation correctors VX-440 and VX-152 in triple combination
regimens with tezacaftor (VX-661) and ivacaftor in people with cystic
fibrosis (CF). The Phase 2 study of VX-440 is designed to evaluate the
safety and efficacy of 4-week dosing of VX-440 in combination with
tezacaftor and ivacaftor in approximately 40 people with CF who have one
F508del mutation and one minimal function mutation and approximately 25
people with two copies of the F508del mutation. The first data from this
study are expected in the second half of 2017 and are intended to
support the initiation of Phase 3 development for VX-440. The Phase 2
study of VX-152 will evaluate 2 weeks of triple combination dosing in
approximately 35 people with CF who have one F508del mutation and one
minimal function mutation and approximately 25 people with two copies of
the F508del mutation. Data from the study of VX-152 are also expected in
the second half of 2017 and are intended to support the initiation of a
longer-duration Phase 2b or registrational program for VX-152.

Vertex has submitted Investigational New Drug applications to the U.S.
Food and Drug Administration (FDA) for both VX-440 and VX-152 and
expects to start both studies by the end of 2016.

Vertex also announced today that it plans to begin Phase 1 development
of an additional next-generation corrector, VX-659, by the end of 2016.
The Phase 1 study is expected to enroll healthy volunteers and will also
include an arm to evaluate triple combination dosing in CF patients who
have one F508del mutation and one minimal function mutation. Based on
data from this study, Vertex plans to start a Phase 2 study of VX-659 in
the second half of 2017. The company also expects to advance a fourth
next-generation corrector into Phase 1 development in 2017.

"We are committed to advancing multiple next-generation correctors in
parallel to bring the best potential treatments to all people with CF
who have at least one F508del mutation," said Jeffrey Chodakewitz, M.D.,
Executive Vice President and Chief Medical Officer at Vertex. "We
believe that the combination of a next-generation corrector with
tezacaftor and ivacaftor has the potential to benefit a broad range of
people with this disease, including those with minimal function
mutations who do not yet have a medicine to treat the underlying cause
of their CF."

"KALYDECO and ORKAMBI are significant medical advances for many people
with CF, however a very large number of our patients still do not have
medicine to treat the cause of their disease," said Patrick Flume, M.D.,
Director of the Medical University of South Carolina Cystic Fibrosis
Center and Principal Investigator for the Phase 2 VX-152 study. "The
studies announced today are a promising step forward for patients and
for the treatment of this devastating disease. I look forward to working
with Vertex to move these potential medicines through development and
toward patients as rapidly as possible."

The initiation of the Phase 2 studies of VX-440 and VX-152 is based on
data from preclinical studies as well as recently completed Phase 1
studies for VX-440 and VX-152 that each enrolled approximately 100
healthy volunteers. Additional details for each Phase 2 study are
provided below.

About the VX-440 Phase 2 Study

The Phase 2 study of VX-440 includes three parts. Part A of the study is
designed to evaluate triple combination dosing for 4 weeks in
approximately 40 patients ages 18 and older with one F508del mutation
and one minimal function mutation. Part B of the study is designed to
evaluate triple combination dosing for 4 weeks in approximately 25
patients ages 18 and older with two copies of the F508del mutation. A
detailed study design is provided in Table 1.

Part A Cohort 1a will evaluate low-dose VX-440 in combination with
tezacaftor and ivacaftor. Cohort 1a is designed to confirm that the
safety and pharmacokinetic properties observed in healthy volunteers are
similar in people with CF. The doses for Part A Cohort 1b and Part B
will be confirmed based on review of data from Part A Cohort 1a.

The primary endpoints of the study are safety and tolerability and the
absolute change in percent predicted forced expiratory volume in one
second (ppFEV1). Secondary endpoints will evaluate relative
improvement in ppFEV1, change in sweat chloride and change in
the CF questionnaire-revised (CFQ-R) respiratory domain score, among
others. Women of childbearing potential who enroll in the Phase 2 study
of VX-440 will be required to use pre-specified, non-hormonal methods of
contraception.

Pending completion of enrollment, Vertex expects to report data from
both cohorts of Part A and from Part B in the second half of 2017. The
initiation of Phase 3 development is pending data from Parts A and B and
discussions with regulatory authorities.

A third part of the study (Part C) is designed to evaluate triple
combination dosing for 12 weeks in approximately 130 patients ages 12
and older with one F508del mutation and one minimal function mutation.
Part C will be initiated based on data from Part A and Part B and would
run in parallel with potential Phase 3 development. Part C is intended
to generate 12-week safety and efficacy data and to demonstrate the
contribution of the components to the overall effect of the triple
combination regimen.

About the VX-152 Phase 2 Study

The Phase 2 study of VX-152 includes two parts. Part A of the study
includes up to three dose escalation cohorts and is designed to evaluate
triple combination dosing for 2 weeks in approximately 35 patients ages
18 and older with one F508del mutation and one minimal function
mutation. Part B of the study includes up to two cohorts and is designed
to evaluate triple combination dosing for 2 weeks in approximately 25
patients ages 18 and older with two copies of the F508del mutation. A
detailed study design is provided in Table 2.

The primary endpoint of the study is safety and tolerability. Secondary
endpoints will evaluate absolute and relative improvement in ppFEV1,
change in sweat chloride, and change in the CFQ-R respiratory domain
score, among others. Part A Cohort 1a, will evaluate low-dose VX-152 in
combination with tezacaftor and ivacaftor. The doses for Part A Cohort
1b, Cohort 1c and Part B will be based on review of data from prior
cohorts.

Pending completion of enrollment, Vertex expects to report data from
Parts A and B of this study in the second half of 2017. These data are
intended to support the initiation of a longer-duration Phase 2b or
registrational program.

Advancing Additional Next-Generation Correctors
into Phase 1

As part of Vertex's commitment to find new medicines to treat the cause
of CF for all people with the disease, the company is evaluating
multiple next-generation correctors in parallel, both in research and
development, to maximize the probability of rapidly advancing the best
regimens to help the greatest number of people with CF. Consistent with
that strategy, Vertex today announced that it plans to begin clinical
development of a third next-generation corrector, VX-659, in 2016.

In human bronchial epithelial (HBE) cells with multiple different CFTR
genotypes, including cells with two copies of the F508del
mutation and cells with one copy of the F508del mutation and one
copy of a mutation known to result in minimal CFTR function, the triple
combination of VX-659, tezacaftor and ivacaftor exhibited higher maximal
efficacy (as measured by percent of normal chloride transport) and
enhanced potency compared to other next-generation correctors in triple
combination.

A Phase 1 study of VX-659 is expected to begin by the end of 2016 and
will evaluate single ascending doses, multiple ascending doses and
triple combination dosing with tezacaftor and ivacaftor in healthy
volunteers. The Phase 1 study will also include an arm to evaluate
triple combination, or placebo, dosing in people with CF who have one
copy of the F508del mutation and one copy of a minimal function
mutation. Pending results of this study, Vertex plans to initiate a
Phase 2 study to evaluate VX-659 in people with CF in the second half of
2017.

In addition to VX-659, Vertex expects to move a fourth next-generation
corrector from research into clinical development in 2017.

INDICATION AND IMPORTANT SAFETY INFORMATION FOR KALYDECO®
(ivacaftor)

KALYDECO (ivacaftor) is a prescription medicine used for the treatment
of cystic fibrosis (CF) in patients age 2 years and older who have one
of the following mutations in their CF gene: G551D, G1244E,
G1349D, G178R, G551S, S1251N, S1255P, S549N,
S549R, or R117H. KALYDECO is not for use in people with CF
due to other mutations in the CF gene. KALYDECO is not effective in
patients with CF with two copies of the F508del mutation (F508del/F508del)
in the CF gene. It is not known if KALYDECO is safe and effective in
children under 2 years of age.

Patients should not take KALYDECO if they are taking certain
medicines or herbal supplements such as: the antibiotics rifampin or
rifabutin; seizure medications such as phenobarbital, carbamazepine, orphenytoin; or St. John's wort.

Before taking KALYDECO, patients should tell their doctor if they:
have liver or kidney problems; drink grapefruit juice, or eat grapefruit
or Seville oranges; are pregnant or plan to become pregnant because it
is not known if KALYDECO will harm an unborn baby; and are breastfeeding
or planning to breastfeed because is not known if KALYDECO passes into
breast milk.

KALYDECO may affect the way other medicines work, and other medicines
may affect how KALYDECO works. Therefore the dose of KALYDECO may
need to be adjusted when taken with certain medications. Patients should
especially tell their doctor if they take antifungal medications such as
ketoconazole, itraconazole, posaconazole, voriconazole, or fluconazole;
or antibiotics such as telithromycin, clarithromycin, or erythromycin.

KALYDECO can cause dizziness in some people who take it. Patients should
not drive a car, use machinery, or do anything that needs them to be
alert until they know how KALYDECO affects them. Patients should avoid
food containing grapefruit or Seville oranges while taking KALYDECO.

KALYDECO can cause serious side effects including:

High liver enzymes in the blood have been reported in patients
receiving KALYDECO. The patient's doctor will do blood tests to
check their liver before starting KALYDECO, every 3 months during the
first year of taking KALYDECO, and every year while taking KALYDECO. For
patients who have had high liver enzymes in the past, the doctor may do
blood tests to check the liver more often. Patients should call their
doctor right away if they have any of the following symptoms of liver
problems: pain or discomfort in the upper right stomach (abdominal)
area; yellowing of their skin or the white part of their eyes; loss of
appetite; nausea or vomiting; or dark, amber-colored urine.

Abnormality of the eye lens (cataract) has been noted in some children
and adolescents receiving KALYDECO. The patient's doctor should perform
eye examinations prior to and during treatment with KALYDECO to look for
cataracts. The most common side effects include headache; upper
respiratory tract infection (common cold), which includes sore throat,
nasal or sinus congestion, and runny nose; stomach (abdominal) pain;
diarrhea; rash; nausea; and dizziness.

These are not all the possible side effects of KALYDECO.

Please click here
to see the full Prescribing Information for KALYDECO (ivacaftor).

INDICATION AND IMPORTANT SAFETY INFORMATION FOR ORKAMBI® (lumacaftor/ivacaftor)
TABLETS

ORKAMBI is a prescription medicine used for the treatment of cystic
fibrosis (CF) in patients age 6 years and older who have two copies of
the F508del mutation (F508del/F508del) in their CFTR gene.
ORKAMBI should only be used in these patients. It is not known if
ORKAMBI is safe and effective in children under 6 years of age.

Patients should not take ORKAMBI if they are taking certain medicines
or herbal supplements, such as: the antibiotics rifampin or
rifabutin; the seizure medicines phenobarbital, carbamazepine, or
phenytoin; the sedatives/anti-anxiety medicines triazolam or midazolam;
the immunosuppressant medicines everolimus, sirolimus, or tacrolimus; or
St. John's wort.

Before taking ORKAMBI, patients should tell their doctor if they: have
or have had liver problems; have kidney problems; have had an organ
transplant; are using birth control (hormonal contraceptives, including
oral, injectable, transdermal or implantable forms). Hormonal
contraceptives should not be used as a method of birth control when
taking ORKAMBI. Patients should tell their doctor if they are pregnant
or plan to become pregnant (it is unknown if ORKAMBI will harm the
unborn baby) or if they are breastfeeding or planning to breastfeed (it
is unknown if ORKAMBI passes into breast milk).

ORKAMBI may affect the way other medicines work and other medicines may
affect how ORKAMBI works. Therefore, the dose of ORKAMBI or other
medicines may need to be adjusted when taken together. Patients should
especially tell their doctor if they take: antifungal medicines such as
ketoconazole, itraconazole, posaconazole, or voriconazole; or
antibiotics such as telithromycin, clarithromycin, or erythromycin.

When taking ORKAMBI, patients should tell their doctor if they
stop ORKAMBI for more than 1 week as the doctor may need to change the
dose of ORKAMBI or other medicines the patient is taking. It is unknown
if ORKAMBI causes dizziness. Patients should not drive a car, use
machinery, or do anything requiring alertness until the patient knows
how ORKAMBI affects them.

ORKAMBI can cause serious side effects including:

High liver enzymes in the blood, which can be a sign of liver injury,
have been reported in patients receiving ORKAMBI. The patient's
doctor will do blood tests to check their liver before they start
ORKAMBI, every three months during the first year of taking ORKAMBI, and
annually thereafter. The patient should call the doctor right away if
they have any of the following symptoms of liver problems: pain or
discomfort in the upper right stomach (abdominal) area; yellowing of the
skin or the white part of the eyes; loss of appetite; nausea or
vomiting; dark, amber-colored urine; or confusion.

Respiratory events such as shortness of breath or chest tightness
were observed in patients when starting ORKAMBI. If a patient has
poor lung function, their doctor may monitor them more closely when
starting ORKAMBI.

An increase in blood pressure has been seen in some patients treated
with ORKAMBI. The patient's doctor should monitor their blood
pressure during treatment with ORKAMBI.

Abnormality of the eye lens (cataract) has been noted in some
children and adolescents receiving ORKAMBI and ivacaftor, a component of
ORKAMBI. For children and adolescents, the patient's doctor should
perform eye examinations prior to and during treatment with ORKAMBI to
look for cataracts.

Please click here
to see the full Prescribing Information for ORKAMBI.

About Vertex

Vertex is a global biotechnology company that aims to discover, develop
and commercialize innovative medicines so people with serious diseases
can lead better lives. In addition to our clinical development programs
focused on cystic fibrosis, Vertex has more than a dozen ongoing
research programs aimed at other serious and life-threatening diseases.

Founded in 1989 in Cambridge, Mass., Vertex today has research and
development sites and commercial offices in the United States, Europe,
Canada and Australia. For six years in a row, Science magazine has named
Vertex one of its Top Employers in the life sciences. For additional
information and the latest updates from the company, please visit www.vrtx.com.

Investor Conference Call and Webcast

Vertex will host a conference call and webcast today at 4:30 p.m. ET to
review its third quarter financial results and also discuss the clinical
development plans for VX-440, VX-152 and VX-659. To access the call,
please dial (866) 501-1537 (U.S.) or +1 (720) 545-0001 (International).
The conference call will be webcast live and a link to the webcast can
be accessed through Vertex's website at www.vrtx.com
in the "Investors" section under "Events and Presentations." To ensure a
timely connection, it is recommended that users register at least 15
minutes prior to the scheduled webcast. An archived webcast will be
available on the company's website.

Special Note Regarding Forward-looking
Statements

This press release contains forward-looking statements as defined in the
Private Securities Litigation Reform Act of 1995, including, without
limitation, Dr. Chodakewitz's statements in the fourth paragraph of the
press release, Dr. Flume's statements in the fifth paragraph of the
press release and statements regarding the expected timing and clinical
trial designs for planned clinical studies of VX-440, VX-152, VX-659 and
any additional next-generation corrector. While Vertex believes the
forward-looking statements contained in this press release are accurate,
these forward-looking statements represent the company's beliefs only as
of the date of this press release and there are a number of factors that
could cause actual events or results to differ materially from those
indicated by such forward-looking statements. Those risks and
uncertainties include, among other things, that data from the company's
development programs may not support further development or registration
of VX-440, VX-152 or VX-659 (including combination regimens containing
such compounds) or its other compounds due to safety, efficacy or other
reasons, and other risks listed under Risk Factors in Vertex's annual
report and quarterly reports filed with the Securities and Exchange
Commission and available through the company's website at www.vrtx.com.
Vertex disclaims any obligation to update the information contained in
this press release as new information becomes available.